IL-17 is a T cell-derived cytokine that plays an important role in the initiation or maintenance of the proinflammatory response(1–5). Recently, four new proteins are identified and termed as IL-17B, IL-17C, IL-17E/IL-25 and IL-17F/ML-1/IL-26 that are clearly related to IL-17, suggesting that there exists a family of IL-17-like molecules (6–13).
Three homologous receptors for IL-17 family members are also identified, termed as IL-17 receptor, IL-17BR (also known as IL-17Rh1) and IL-17RL (14). IL-17 receptor (IL-17AR) located on human chromosome 22q11.22–11.23 is widely expressed in different tissues and is reported to bind to IL-17A with a weaker affinity than the potency of IL-17A on responsive cells. This receptor is shown to regulate the activities of extracellular regulated kinase ERK1, ERK2, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase, Raf-1 kinase, STATs and NF-κB (15–20). Furthermore, the recent report that IL-17AR signaling is deficient in TRAF-6-deficient cells strongly suggests that members of the TRAF family, known to be involved in both IL-1/Toll and TNF receptor signaling, are also involved in IL-17AR signaling (21). The proinflammatory function and intracellular signaling pathway of IL-17AR are strikingly similar to those of the IL-1 and Toll receptors (22–26). IL-17BR (IL-17Rh1) located on human chromosome 3p21.1 is expressed mostly in liver and kidney tissues. This receptor binds to IL-17B and IL-17E but not IL-17A (8). Moreover this receptor is shown to activate NF-κB only by luciferase assay in vitro. IL-17RL located on human chromosome 3p25.3–3p24.1 is expressed mainly in prostate, cartilage, kidney, liver, heart, and muscle tissues (14), which has at least eleven splicing forms. However, the signaling mechanism and the biological functions of this receptor are still unknown.
Thus so, in an attempt to identify new IL-17 receptor like membrane proteins, the inventors have isolated and identified a novel single span transmembrane type 1 cytokine receptor-like protein with 31% amino acid identity to IL-17 receptor, and designated the new receptor as hIL-17RLM (IL-17 receptor like molecule).